The present invention relates generally to interstitial fluid monitoring equipment and is particularly directed to a portable glucose monitoring system of the type which could be used at home by consumers. The invention is specifically disclosed as a home glucose monitoring system that uses an array of microneedles to painlessly sample interstitial fluid and provide an indication of the glucose concentration.
Topical delivery of drugs and topical sampling of biological fluids are very useful methods for achieving either systemic or localized pharmacological effects, or for diagnostics, although there is a main challenge involved in providing sufficient fluid penetration across the skin. Skin consists of multiple layers, in which the stratum corneum layer is the outermost layer, then a viable epidermal layer, and finally a dermal tissue layer. The thin layer of stratum corneum represents a major barrier for chemical penetration through the skin. The stratum corneum is responsible for 50%-90% of the skin barrier property, depending upon the analyte""s water solubility and molecular weight.
An alternative to the use of hypodermic needles for drug delivery by injection is disclosed in U.S. Pat. No. 3,964,482 (by Gerstel), in which an array of either solid or hollow microneedles is used to penetrate through the stratum corneum and into the epidermal layer. Fluid is dispensed either through the hollow microneedles or through permeable solid projections, or perhaps around non-permeable solid projections that are surrounded by a permeable material or an aperture. A membrane material is used to control the rate of drug release, and the drug transfer mechanism is absorption.
Other types of microneedle structures are disclosed in WO 98/00193 (by Altea Technologies, Inc.), and in WO 97/48440, WO 97/48441, and WO 97/48442 (by Alza Corp.). In addition, WO 96/37256 discloses another type of microblade structure. Moreover, WO 99/64580 and WO 00/74763 A2, by Georgia Tech Research Corporation, disclose various microneedle structures and methods for manufacturing the same.
The use of microneedles has one great advantage in that intracutaneous drug delivery or drug sampling can be accomplished without pain and without bleeding. As used herein, the term xe2x80x9cmicroneedlesxe2x80x9d refers to a plurality of elongated structures that are sufficiently long to penetrate through the stratum corneum skin layer and into the epidermal layer. In general, the microneedles are not to be so long as to penetrate into the dermal layer, although there are circumstances where that would be desirable.
A portable microneedle device that can extract or inspect interstitial fluid from skin and provide an instantaneous readout on a display would be very useful, particularly for diabetics who desire to know in real time their glucose level (concentration). It would be very advantageous to provide one or more self-contained sampling devices based upon microneedles that make available a xe2x80x9cmicroneedle patchxe2x80x9d or xe2x80x9cmicroneedle stripxe2x80x9d that a human user can touch (with a finger, for example), then press an actuator button or switch to inspect or extract a fluid sample, and finally that automatically display the results, in real time or near-real time. It would be further desirable if the microneedle portions were disposable, designed for a single use.
Accordingly, it is an advantage of the present invention to provide a fluid sampling apparatus that includes a plurality of microneedles accessible on a first surface, a manually-operated pumping apparatus accessible on a second surface, and a reservoir that is in hydraulic communication with both the microneedles and the pumping apparatus. The reservoir receives fluid that flows through the plurality of microneedles upon manual actuation of the pumping apparatus.
It is another advantage of the present invention to provide a fluid sampling apparatus that includes a plurality of solid, coated microneedles accessible on a first surface, a member having a first end near the coated microneedles and which extends to a second end distal from the coated microneedles, and at least one electrode positioned on the extending member, in which the electrodes are in communication with the coated microneedles. The solid microneedles are coated on an exterior surface, and the coating on the microneedles acts as an electrochemical sensor of a property of a fluid of a biological barrier such as skin. When the solid microneedles make contact with the biological barrier, the electrochemical sensor generates an electrical signal in response to the fluid property.
It is a further advantage of the present invention to provide yet another fluid sampling apparatus that includes an attachable/detachable portion that has a plurality of microneedles, a reservoir, an optical sensor pad, and an optical window; and a main body portion that includes a receptacle to receive the attachable/detachable portion such that, when in position, the optical window faces the main body portion and the plurality of microneedles are accessible, a light source and light detector, and a manually-operated control actuator mounted on a surface of the main body portion that causes fluid to flow proximal to the plurality of microneedles. The reservoir receives fluid that flows through the plurality of microneedles upon manual operation of the control actuator, and the optical sensor pad exhibits a change in a physical property that is detected by the light detector as the light source shines light upon the optical sensor pad.
It is a still further advantage of the present invention to provide still another fluid sampling apparatus is provided, which includes an attachable/detachable portion that has a plurality of microneedles, a reservoir, an electrochemical sensor pad, and at least one electrode in communication with the sensor pad; and a main body portion that includes a receptacle to receive the attachable/detachable portion such that, when in position, the electrodes face the main body portion and the plurality of microneedles are accessible, an electron sensor, and a manually-operated pumping apparatus accessible on a surface of the main body portion. The reservoir receives fluid that flows through the plurality of microneedles upon manual actuation of the pumping apparatus, and the electrochemical sensor pad exhibits a change in a physical property that is detected by the electrodes, which output an electrical signal. The electron sensor is in communication with the electrodes and generates an output signal in response to the electrical signal.
It is still another advantage of the present invention to provide a fluid sampling apparatus that includes a plurality of microneedles and an associated substrate that is in mechanical communication with a manually operable plunger, a housing that contains a variable volume chamber and which contains a flexible membrane that deflects upon movement of the plunger, in which the membrane""s deflection causing a variation in the volume of the chamber, and an output port that is in hydraulic communication with the variable volume chamber. Upon actuation of the plunger in one direction, the microneedles are pushed into and pierce a biological barrier such as skin. Upon actuation of the plunger in a second, opposite direction, fluid from the biological barrier is withdrawn into the variable volume chamber and thereby directed to the output port.
It is yet a further advantage of the present invention to provide a replaceable cartridge that includes a plurality of microneedle strips attached to a movable substrate of material; in which each of the microneedle strips includes a plurality of microneedles accessible to a user, a sensor that is in communication with a fluid that flows through the microneedles, and a signal transducer that is in communication with the sensor. The signal transducer of a first of the plurality of microneedle strips generates an electrical signal that is communicated to an output port. The movable substrate or web of material is indexable to a xe2x80x9cnextxe2x80x9d position that will make a second of the plurality of microneedle strips accessible to a user.
It is yet another advantage of the present invention to provide a single-use microneedle system that comprises: an array of microneedle members that protrude from a base member, the microneedle members being of a size, shape, and material so as to penetrate through a stratum corneum of skin when placed against the skin; and a self-destruct mechanism that renders the microneedle members incapable of penetrating the stratum corneum after being operative upon the microneedle members, the self-destruct mechanism comprising one of: (a) a heat source, (b) an electrical energy source, (c) an optical energy source, (d) a chemical reaction, (e) a mechanical member that exerts a force, or (f) a material that permanently encapsulates the microneedle members.
Additional advantages and other novel features of the invention will be set forth in part in the description that follows and in part will become apparent to those skilled in the art upon examination of the following or may be learned with the practice of the invention.
To achieve the foregoing and other advantages, and in accordance with one aspect of the present invention, a fluid sampling apparatus is provided, comprising: (1) a plurality of microneedles accessible on a first surface of the fluid sampling apparatus; (2) a manually-operated pumping apparatus accessible on a second surface of the fluid sampling apparatus; and (3) a reservoir that is in hydraulic communication with both the plurality of microneedles and the pumping apparatus. The reservoir receives fluid that flows through the plurality of microneedles upon manual actuation of the pumping apparatus.
In accordance with another aspect of the present invention, a fluid sampling apparatus is provided, comprising: (1) a plurality of solid microneedles accessible on a first surface of the fluid sampling apparatus, in which the solid microneedles are coated on an exterior surface; (2) when the solid microneedles make contact with a biological barrier, the coating on the microneedles acts as an electrochemical sensor of a property of a fluid of the biological barrier, and the electrochemical sensor generates an electrical signal in response to the fluid property; (3) a member having a first end near the coated microneedles and which extends to a second end distal from the coated microneedles; and (4) at least one electrode positioned on the extending member, in which the electrode(s) is/are in communication with the coated microneedles.
In accordance with a further aspect of the present invention, a fluid sampling apparatus is provided, comprising: (1) an attachable/detachable portion that includes a plurality of microneedles, a reservoir, an optical sensor pad, and an optical window; and (2) a main body portion that includes: (a) a receptacle to receive the attachable/detachable portion such that, when in position, the optical window faces the main body portion and the plurality of microneedles are accessible; (b) a light source and light detector; and (c) a manually-operated control actuator mounted on a surface of the main body portion that causes fluid to flow proximal to the plurality of microneedles. The reservoir receives fluid that flows through the plurality of microneedles upon manual operation of the control actuator, and the optical sensor pad exhibits a change in a physical property that is detected by the light detector as the light source shines light upon the optical sensor pad.
In accordance with a yet further aspect of the present invention, a fluid sampling apparatus is provided, comprising: (1) an attachable/detachable portion that includes a plurality of microneedles, a reservoir, an electrochemical sensor pad, and at least one electrode in communication with the sensor pad; and (2) a main body portion that includes (a) a receptacle to receive the attachable/detachable portion such that, when in position, the electrode(s) face(s) the main body portion and the plurality of microneedles are accessible; (b) an electron sensor; and (c) a manually-operated pumping apparatus accessible on a surface of the main body portion. The reservoir receives fluid that flows through the plurality of microneedles upon manual actuation of the pumping apparatus, and the electrochemical sensor pad exhibits a change in a physical property that is detected by the electrode(s), which output(s) an electrical signal. The electron sensor is in communication with the electrode(s) and generates an output signal in response to the electrical signal.
In accordance with a still further aspect of the present invention, a fluid sampling apparatus is provided, comprising: (1) a plurality of microneedles and an associated substrate that is in mechanical communication with a manually operable plunger; (2) a housing that contains a variable volume chamber and which contains a flexible membrane that deflects upon movement of the plunger, in which the membrane""s deflection causing a variation in the volume of the chamber; and (3) an output port that is in hydraulic communication with the variable volume chamber. Upon actuation of the plunger in one direction, the microneedles are pushed into and pierce a biological barrier such as skin. Upon actuation of the plunger in a second, opposite direction, fluid from the biological barrier is withdrawn into the variable volume chamber and thereby directed to the output port.
In accordance with a still another aspect of the present invention, a replaceable cartridge is provided, comprising: (1) a plurality of microneedle strips attached to a movable substrate of material, in which each of the microneedle strips includes: (a) a plurality of microneedles accessible to a user, (b) a sensor that is in communication with a fluid that flows through the microneedles, and (3) a signal transducer that is in communication with the sensor. The signal transducer of a first of the plurality of microneedle strips generates an electrical signal that is communicated to an output port. The movable substrate or web of material is indexable to a xe2x80x9cnextxe2x80x9d position that will make a second of the plurality of microneedle strips accessible to a user.
In accordance with a yet a further aspect of the present invention, a single-use microneedle system is provided, comprising: an array of microneedle members that protrude from a base member, the microneedle members being of a size, shape, and material so as to penetrate through a stratum corneum of skin when placed against the skin; and a self-destruct mechanism that renders the microneedle members incapable of penetrating the stratum corneum after being operative upon the microneedle members, the self-destruct mechanism comprising one of: (a) a heat source, (b) an electrical energy source, (c) an optical energy source, (d) a chemical reaction, (e) a mechanical member that exerts a force, or (f) a material that permanently encapsulates the microneedle members.
Still other advantages of the present invention will become apparent to those skilled in this art from the following description and drawings wherein there is described and shown a preferred embodiment of this invention in one of the best modes contemplated for carrying out the invention. As will be realized, the invention is capable of other different embodiments, and its several details are capable of modification in various, obvious aspects all without departing from the invention. Accordingly, the drawings and descriptions will be regarded as illustrative in nature and not as restrictive.